I. The Field of the Invention
This invention relates to solid-state chemical sensors, and more particularly to a solid-state chemical sensor fabricated on an integrated circuit. An embodiment is included in which the integrated circuit incorporates a plurality of chemical-selective sensors, and related circuitry, for producing an output voltage corresponding to the chemical activity found at one or more of the sensors.
II. The Prior Art
A. Historical Development
One of the most active research areas in the field of analytical measurement is the development of chemical sensors with selectivity for specific ions, gases, biological materials and other substances. Ion selective electrodes (ISEs) have been in use since the discovery, early in this century, of the ion selective properties of the glass/electrolyte interface. ISEs have been popular because of their relatively low cost, wide dynamic range, ease of use and versatility.
During the past decade, a new generation of miniaturized solid-state chemical sensors has evolved which are the progeny of electrochemistry and solid-state electronics. Development of these solid-state chemical transducers was originally motivated by the need for better monitoring of ion activity in biological environments. Medical uses are still seen as among the most promising applications for these solid-state chemical transducers, with researchers hoping to monitor a variety of electrolytes, blood gases, immunochemical agents, and metabolic substrates. Such miniaturized, implantable chemical sensors can aid in the study of biochemical processes and serve as the transducers in biochemical control systems, as well as helping physicians to make proper diagnoses and to maintain homeostasis in critically ill patients.
In addition to the desirable features of the ion selective electrode, the new generation of miniaturized solid-state chemical transducers has the added advantages of inherent impedance transformation, which reduces electrical noise, as well as miniaturization and potentially low-cost mass production made possible through the use of integrated circuit manufacturing processes. Thus, in addition to their use in biochemical applications, miniaturized solid-state chemical transducers are also beginning to be recognized as having many potentially useful applications in addition to biochemistry, such as monitoring pollutants in the atmosphere, public water supplies and industrial effluents; measuring hardness in boiler feed waters; on-line analysis of industrial processes such as electroplating, photographic processing, and the manufacture of foodstuffs and medicines; and in analytical laboratory instruments. In short, while there remain certain restrictions on the chemicals which can be detected using these solid-state chemical sensors, nevertheless many applications in medical and industrial instrumentation could greatly benefit from the use of such miniaturized solid-state chemical transducers.
B. CHEMFET Features
One of the most studied and most successful sensors from this new generation of miniaturized solid-state chemical transducers has been the chemical sensitive field-effect transistor, or CHEMFET. The structure and operation of the CHEMFET is similar in many ways to the structure and operation of a customary insulated gate field-effect transistor, or IGFET. A simplified diagram showing the structure of a CHEMFET is depicted in FIG. 1. This diagram is representative of the CHEMFETS that can be found in the prior art and is essentially the device described in U.S. Pat. No. 4,020,830 issued to C. C. Johnson, S. D. Moss and J. Janata entitled "Selective Chemical Sensitive FET Transducers." This patent presents a detailed review of the theory, structure, and operation of the CHEMFET as found in the prior art.
An appreciation of the operation of the present invention and its advantages over the devices found in the prior art will be gained by a brief review of the operation and structure of the CHEMFET. CHEMFET's are made by substituting a chemical-selective membrane as indicated at 10 in FIG. 1, for what would otherwise be the gate electrode of an IGFET. The membrane 10 is designed to interact with certain species of chemicals to develop an electrical potential at the membrane/gate of the CHEMFET, or to change the threshold voltage of the field-effect transistor. In either case the gate-minus-threshold voltage (V.sub.G -V.sub.T) is modified.
In the CHEMFET shown in FIG. 1, the CHEMFET is formed using silicon semiconductor fabrication techniques well-known in the art. The silicon substrate is indicated at 8. The substrate 8 is grown with a p-type dopant and into this p-type semiconductor material is diffused two n-type regions, the source 7 and the drain 6. Conductors 7a and 6a are attached to the source and drain regions 7 and 6, and serve as the source and drain terminals. An insulating layer 12 is deposited such that the source and drain terminals 7a and 6a do not contact the p-type substrate 8. An insulating layer 5 is grown with thermal oxidation over substrate 8 in the region between the source and drain diffusion regions 7 and 6. Another insulating layer 5a is also applied over the source and drain terminal conductors 7a and 6a. The area 9 of the substrate 8 between the source and drain diffusion regions 7 and 6 is called the channel region. The insulating layer 5 applied to the substrate 8 above the channel region 9 is termed the gate insulator.
The chemical-selective membrane 10 is applied to the gate insulator 5 in the area above the channel region 9. The membrane 10 occupies the same area as would the gate electrode in a customary insulating gate field-effect transistor. A final encapsulating layer 4 is applied to the exposed surface of the device except for the top portion 11 of membrane 10. Layer 4 provides electrical isolation and prevents the fluid 2 in container 3, into which the CHEMFET is placed, from making electrical contact with internal circuit parts of the CHEMFET.
With the CHEMFET shown in FIG. 1, the membrane 10 electrically responds when a certain chemical, or group of chemicals, contacts the membrane 10 thus causing a corresponding modulation of the electric field through the gate insulator 5, and consequently a modulation of conductivity in the channel region 9 of the transistor. In this way the electrical response of the CHEMFET represents the chemical activity (i.e., concentration of ionized chemical) found at the surface 11 of membrane 10. A reference electrode 1 is placed into the fluid so as to provide a reference against which the CHEMFET's voltage measurements may be compared.
Three different types of chemical-selective membranes have been proposed for use in solid-state chemical sensors. The first of these senses electrically neutral molecules. The presence of electrically neutral molecules reversibly changes the work function of certain gate materials which absorb them. Materials such as palladium, platinum, and nickel have been tested as gate materials. For example, hydrogen and compounds of hydrogen have been successfully sensed using palladium as the gate material. The work function of palladium (the term work function referring to the potential required to cause emission of an electron from the surface of a material) has been shown to change by 1,240 millivolts when exposed to hydrogen at a pressure of one atmosphere.
A second suggested type of membrane material used for measuring chemical activity with a solid-state chemical sensor is based upon solution/insulator interface theory utilizing polarized interfaces. The potential across the solution/membrane interface is a function of charge which accumulates on the solution side of the interface. With such a membrane, excess charge density on the surface of the interface will be related to chemical activity in a predictable way. However, polarized interface materials presently available in the art have not yet proven to be practical for use in analytical applications.
A third type of chemical-selective membrane material employs a semi-permeable membrane. The membrane is designed to allow certain charged molecules to cross the membrane/solution interface while blocking others. Membranes of this type are referred to as ion-selective membranes. The charged molecules, or ions, migrate across the semi-permeable surface of the membrane until an equilibrium is reached where enough ions have migrated into or out of the membrane to make the electrochemical potential of the ions in the membrane equal to the electrochemical potential of ions in the fluid being analyzed. The potential created by migration of the ions is utilized to modulate the channel region 9 and hence the electric signal produced by the chemical sensor. When the potential found at the chemical sensor is compared to the voltage of a reference electrode placed in the same fluid as the membrane, the activity of the particular ion to which the membrane responds may be readily determined since the membrane voltage is related to the activity of the ion by a simple logarithmic relationship.
Of the three chemical-selective membrane types found in the prior art, the ion-selective membrane has been used most successfully to date. A wide variety of materials for use in ion-selective membranes have been used to sense ions of hydrogen, potassium, calcium, sodium, ammonium, fluoride, and other ions. Furthermore, ion-selective membranes present the possibility that more complex molecules can be detected by using an enzyme or bacterial overlay on the ion-selective membrane where one of the products of the action of the enzyme or bacteria is that to which the ion-selective membrane responds. As used hereinafter, the term chemical-selective membrane is hereby defined to mean any chemical-selective material which is capable of producing an electrical signal that is linearly or non-linearly proportional to a concentration of at least one chemical.
Compared to conventional methods of chemical analysis, solid-state sensors such as the CHEMFET provide a number of advantages, including small size, solid-state construction, inherent impedance transformation, and comparatively low cost. The small size of miniaturized solid-state chemical sensors opens up the possibility of in vivo monitoring of biological fluids. When used for in vivo monitoring, miniaturized sensors may be mounted on a catheter and inserted directly into a patient's blood vessel, or other body structure, to provide constantly updated reports on the patient's blood chemistry or analysis of other body fluid.
Furthermore, a miniaturized chemical sensor has advantages when used for in vitro applications, such as in analytical laboratory measurements. These advantages include: allowing the use of smaller samples; lower device capacitances which allow higher bandwith operation; and a smal sensing surface allowing tracking of local changes in chemical activity rather than averaging chemical activity over a large area. Furthermore, only a small amount of chemical-selective membrane material is needed which can be very important when such materials are expensive. Thus, the advantages of a miniaturized solid-state chemical sensor over other analytical methods are potentially so numerous that in recent years a great deal of research has been devoted toward the development of miniaturized solid-state sensors, miniaturization being an important goal in order to increase the number of potential applications of solid-state chemical sensors.
Solid-state chemical sensors provide other advantages including the fact that solid-state construction provides a mechanically robust sensor which can be used in high pressure, or high vibration environments. Also, since the solid-state chemical sensor is not filled with fluid, as compared to conventional ion-selective electrodes, high temperature operation is possible. Still further, sterilization of solid-state chemical sensors for use in medical applications is easier because no filling fluid is involved.
C. Problems and Shortcomings of the Prior Art
Despite these potential advantages, solid-state chemical sensors presently available in the art suffer from several serious drawbacks which have prevented such sensors from being fully utilized in industrial, scientific and medical applications. These problems include errors introduced into the sensor's output signal due to imperfectly selective membranes or due to signal drift because of aging, temperature or ambient light conditions, and difficulties in fabricating the sensors.
1. Signal Error Due to Imperfectly Selective Membranes
One of the difficulties encountered is that the electric signal derived from a solid-state chemical sensor is typically subject to error signals from several sources. One of these sources stems from the fact that no membrane is perfectly selective to a particular chemical or ion and the electric signal provided by the chemical-selective membrane will include responses due to interfering chemicals. This interference is a serious limitation and it compromises the accuracy of such sensors. This means, for example, that a CHEMFET made to respond to pH might also show a response to sodium. Thus, using a single ion-selective electrode or other chemical sensor in an environment containing two substances to which the chemical-selective membrane responds creates a situation in which there is one equation and two unknowns.
Efforts have been made in the prior art to solve this problem in connection with ion-selective electrodes by using a variation of null point potentiometry which is compensated for interferences, called concentration matching. This technique requires that the test sample be split into two parts, each of which is probed by the same type of sensor. Differences in the ion selective electrodes are taken into account by noting the difference in membrane potentials with identical samples. This provides the so-called null point. One of the ion selective electrodes is then placed in a solvent, to which is added analyte and interferant until the null point is again reached. Arriving at the correct blend of concentrations can only be done by using a simplex optimization, or a polynomial equation solving routine to guide the additions. This procedure is tedious but in the past has been the most successful technique for dealing with interferences in ion selective electrode analysis. However, this technique is ill suited for use with the new miniaturized solid-state chemical sensors, which, as mentioned, hold the promise of continuous monitoring of chemical changes, both in vivo and with flow injection analysis. Concentration matching is neither a real-time process, nor can it be done in vivo.
Another approach to solving the problem of error signals which are caused by interfering ions arises from the possibility of making probes with multiple sensors, so that the interferences can be resolved. For example, if a probe had a second sensor with different sensitivities to one or both of the chemicals involved, two equations would be produced, allowing solution for both unknowns. While this approach potentially holds promise and has been discussed for years, the full development of multisensors has been impeded by: the number of contacts required for parallel connection to the sensors; the time delay to stable operation if sensors and reference voltage are multiplexed; the amount of area on an integrated circuit taken up by a CHEMFET in order to improve transconductance; and limitations on gate size and gate-to-contact spacing for application of certain ion selective membranes. Thus, to date there has not been a satisfactory solution to the problem of compensating for noise signals from interfering ions when using ion selective membranes.
2. Signal Error Due to Drift
Another source of error when using a CHEMFET or solid-state chemical sensor arises because of signal drift with time, temperature and ambient light. The characteristic drift with time has been attributed to mass transport and potential-dependent interfacial ion-crossing kinetics. Thermal sensitivity and photo-induced junction currents cause calibration drifts with ambient changes. Efforts to eliminate light and temperature sensitivity with on-chip compensating circuitry have not been entirely successful because of the inability to precisely match the electrical characteristics (e.g., transconductance) of the CHEMFET to metal oxide semiconductor field effect transistors (MOSFETS) which are typically placed on the integrated circuit to provide compensation. Moreover, since the output signal from a CHEMFET is current, errors can also be introduced by the source and drain resistances, which are also functions of temperature.
3. Fabrication Difficulties
In addition to the above-mentioned problems, other problems which have impeded the use of solid-state chemical sensors such as the CHEMFET have arisen because of fabrication difficulties. One of the principal problems with respect to fabrication arises because of the need for an encapsulation layer which is required to prevent electrical leakage and chemical attack at the sides and back of the sensor when it is exposed to its working environment. These encapsulation procedures are typically manual operations which are extremely difficult to perform with uniformity of results. Another problem is that preparation of the membrane definition layer into which the chemical-selective membrane is deposited and held is also typically a non-planar, manual process. Since solid-state chemical sensors such as the CHEMFET has thus far shown relatively short lifetimes, reducing manufacturing costs is vital to their economic feasibility. More efficient methods of encapsulation and membrane definition are therefore essential.
In summary, the problems discussed above have posed significant obstacles to the wide-scale adoption and use of solid-state chemical sensors, and in particular CHEMFETS, as a practical method of chemical analysis.